1,720,974 research outputs found
The extracellular calcium-sensing receptor and cell-cell signaling in epithelia
No full textIn multicellular organisms, cells are crowded together in organized communities, surrounded by an interstitial fluid of extremely limited volume. Local communication between adjacent cells is known to occur through gap junctions in cells that are physically connected, or through the release of paracrine signaling molecules (e.g. ATP, glutamate, nitric oxide) that diffuse to their target receptors through the extracellular microenvironment. Recent evidence hints that calcium ions may possibly be added to the list of paracrine messengers that allow cells to communicate with one another. Local fluctuations in extracellular [Ca2+] can be generated as a consequence of intracellular Ca2+ signaling events, owing to the activation of Ca2+ influx and efflux pathways at the plasma membrane. In intact tissues, where the interstitial volumes between cells are much smaller than the cells themselves, this can result in significant alterations in external [Ca2+]. This article will explore emerging evidence that these extracellular [Ca2+] changes can be detected by the extracellular calcium-sensing receptor (CaR) on adjacent cells, forming the basis for a paracrine signaling system. Such a mechanism could potentially provide CaR-expressing cells with the means to sense the Ca2+ signaling status of their neighbors, and expand the utility of the intracellular Ca2+ signal to a domain outside the cell
The role of Store-Operated Cyclic AMP Signalling (SOcAMPS) in cardiac physiology and pathology
No full textStore-Operated Cyclic AMP Signaling (SOcAMPS) represents a novel signaling mechanism in which depletion of Ca2+ in the endoplasmic reticulum (ER) leads to a STIM1- dependent (Stromal Interaction Molecule 1) increase in cAMP levels, independently of cytosolic Ca2+.
Here we aimed to evaluate whether SOcAMPS was manifest in neonatal rat ventricular myocytes (NRVM) and human "iCardiomyocytes" and exploit its potential role in cardiac cell hypertrophy.
cAMP levels and ER [Ca2+]were monitored by live cell fluorescence imaging after transfection with the EPAC H30 and D1ER cameleon probes, respectively.
The existence of SOcAMPS in NRVM was first assessed by using the low affinity Ca2+ chelator TPEN, able to induce a reduction of SR Ca2+ levels without affecting cytosolic [Ca2+]. TPEN (1mM) was shown to induce significant cAMP increases both in the absence and presence of 5 M Forskolin (FRSK). Depletion of SR by ionomycin (10 M) was found to exert similar effects. Similar data were obtained in human "iCardiomyocytes".
The participation of STIM1 in the observed phenomenon was proven in NRVM by the 47% reduction of the [cAMP] response obtained after shRNA-mediated knockdown of STIM1. Interestingly, a significant increase of the TPEN+FRSK induced response was found after "in vitro" induced cell hypertrophy.
These data establish, for the first time, the existence of SOcAMPS in the two cardiac cell models analyzed and suggest a potential role for this new signaling mechanism in cardiac cell hypertrophy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Deoxycholic acid activates protein kinase C (PKC) and phospholipase C (PLC) via increased Ca2+ entry at plasma membrane
No full textBackground & Aims: Secondary bile acids like deoxycholic
acid (DCA) are well-established tumor promoters
that may exert their pathologic actions by interfering
with intracellular signaling cascades. Methods: We evaluated
the effects of DCA on Ca2 signaling in BHK-21
fibroblasts using fura-2 and mag-fura-2 to measure cytoplasmic
and intraluminal internal stores [Ca2], respectively.
Furthermore, green fluorescent protein (GFP)-based
probes were used to monitor time courses of phospholipase
C (PLC) activation (pleckstrin-homology [PH]-PLC-
GFP), and translocation of protein kinase C (PKC) and a
major PKC substrate, myristolated alanine–rich C-kinase
substrate (MARCKS). Results: DCA (50–250 mol/L)
caused profound Ca2 release from intracellular stores of
intact or permeabilized cells. Correspondingly, DCA increased
cytoplasmic Ca2 to levels that were 120% of
those stimulated by Ca2-mobilizing agonists in the
presence of external Ca2, and 60% of control in
Ca2-free solutions. DCA also caused dramatic translocation
of PH-PLC-GFP, and conventional, Ca2/diacylglycerol
(DAG)-dependent isoforms of PKC (PKC-I and
PKC-), and MARCKS-GFP, but only in Ca2-containing
solutions. DCA had no effect on localization of a novel
(PKC) or an atypical (PKC) PKC isoform. Conclusions:
Data are consistent with a model in which DCA directly
induces both Ca2 release from internal stores and persistent
Ca2 entry at the plasma membrane. The resulting
microdomains of high Ca2 levels beneath the
plasma membrane appear to directly activate PLC, resulting
in modest InsP3 and DAG production. Furthermore,
the increased Ca2 entry stimulates vigorous recruitment
of conventional PKC isoforms to the plasma
membrane
A reassessment of the effects of luminal [Ca2+] on inositol 1,4,5-trisphosphate-induced Ca2+ release from internal stores
No full text
Deoxycholic acid activates protein kinase C (PKC) and phospholipase C (PLC) through increased Ca2+ entry at plasma membrane
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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